The overall purpose of this study is to investigate the effects of prenatal exposure to ethanol on the development of the central nervous system (CNS) using the hippocampus of the rat as a comprehensive model system. Although this aspect of the Fetal Alcohol Syndrome (FAS) is of obvious theoretical and potentially practical importance, it has received little attention. Utilizing a multidisciplinary approach, the proposal addresses some of the fundamental questions related to the etiology of the Fetal Alcohol Syndrome-related changes in the CNS: 1. What are the effects of various blood alcohol concentrations on the development of the hippocampal formation? 2. What is the minimum ethanol dose, below which no detectable hippocampal damage will occur? 3. What are the "critical" periods when hippocampal development is most vulnerable to ethanol? 4. Is a high blood alcohol level a risk to CNS development even if it occurs for short or intermittent periods such as would be encountered in "binge" drinking? 5. At lower blood alcohol levels do hippocampal abnormalities or developmental delay occur in the absence of other forms of FAS-associated skeletal or soft tissue disrphology? Subsequent to prenatal exposure to ethanol, offspring will be screened for structural and functional alterations using a battery of neuroanatomical, neurochemical and neurophysiological techniques. The neuroanatomical analysis will investgate changes in hippocampal organization and development of neurons and astroglia, acetylcholinesterase staining patterns, and afferent fibers. The development of endogenous levels and responsiveness of cyclic GMP will be determined by the radioimmunoassay method. Neurophysiological parameters to be tested include the organization, functional synaptic development and potentiation of extracellularly recorded mono- and polysynaptic evoked potentials, and multiple unit activity. These experiments will provide basic data on the etiology of the Fetal Alcohol Syndrome as well as information that may be useful in establishing guidelines for safe levels of alcohol consumption by pregnant women.